PCB126暴露による次世代ラットの卵胞発育阻害の機序を明らかにするため,妊娠15日目のSD系雌ラットに30及び100μg/kgのPCB126またはコーン油を単回経口投与し,10～24日齢の出生仔の卵巣における卵胞発育,ステロイド産生関連遺伝子の発現そして血中ホルモン濃度を対照群の動物のそれらと統計学的に比較した。100μg/kg投与群の卵巣では15日齢で小型胞状卵胞,24日齢では小型胞状卵胞及び大型胞状卵胞ともに少なかった。投与群における血中のホルモンは15日齢においてinhibin,estradiol-17βの値が低く,FSH値は高かった。21,24日齢においてもinhibin濃度は低かった。100μg/kg投与群では,卵巣におけるP450sccと3β-HSDの遺伝子発現量が10日齢から低置を示し,15日齢では3β-HSDと17β-HSD遺伝子,21,24日齢ではP450scc,3β-HSD,P450c17,StAR,の遺伝子発現量が少なかった。以上より,PCB126の経胎盤・経乳汁暴露が,次世代幼若ラット卵巣において卵胞発育を阻害して健常な卵胞の数を減少させ,ステロイド合成関連遺伝子の発現量を変化させること,また,血中ホルモン濃度にも影響を及ぼし生殖内分泌機能を撹乱することが示された。

To clarify the mechanisms of growth disturbance of the ovarian follicles in PCB 126-exposed female progeny, the pregnant female SD rats were given single oral administration of corn oil or 30 and 100μg/kg of PCB 126 on gestational day 15. The offspring were sacrificed on the post-natal day (PND) 5-24, and their ovaries were collected for quantification of the gene expression and for counting ovarian follicles. In the ovaries of 100μg/kg-exposed rats, the number of early antral follicles was smaller than that of controls on PND 15. Both early antral and antral follicles were less numerous than those in control rats on PND 24.The levels of mRNA of P450scc and 3β-HSD in the ovaries of 100μg/kg-exposed rats had been lower than those in control animals from PND 10. These exposed rats showed lower level of mRNA of 3β-HSD and 17β-HSD on PND 15, and also lower gene expression of P450scc, 3β-HSD, P450c17 and StAR on PNDs 21 and 24 as compared to control rat ovaries. The values of serum concentration of inhibin and estradiol-17β were lower and that of FSH was higher in exposed rats as compared to those in control rats on PND 15. The value of serum Inhibin was still low in the exposed rats on PNDs 21 and 24.These data suggest that in utero and lactational exposure to PCB 126 disturbs growth of ovarian follicles resulting in decrease of the number of healthy follicles, and modify expression of steroid-relating genes in the ovary of the progeny. In addition, PCB 126 affects serum concentration of some hormones and might disrupt reproductive endocrine mechanisms.

麻布大学ハイテク・リサーチ・センター研究プロジェクト 研究サブ・グループ1

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